Work in this laboratory over the past thirty years has demonstrated that group A streptococci share a number of antigenic determinants with a variety of host tissues especially with respect to the disease rheumatic fever (RF). The recent finding that those individuals susceptible to contracting rheumatic fever have a genetic marker on their B-cells raises the interesting question of what role this B-cell antigen plays in the disease process and how it might influence the host's abnormal immune response to these cross-reactive streptococcal/mammalian antigens. The present proposal will therefore concentrate on the following areas of investigation: 1. to continue our surveys of the B-cell marker in RF patients and other individuals. We will also determine whether antigen expression is influenced by streptococcal infections,immunosuppressive agents and whether it is present in other presumed autoimmune diseases. 2. To continue our efforts to isolate and characterize the D8/17 antigen expressed on certain B-cell lines. 3. To search for the gene encoding the D8/17 antigen in cDNA libraries obtained from the B-cell lines expressing the antigen. 4. To continue our efforts on determining what role the D8/17 antigen plays in the cellular immune response to streptococcal antigens in RF and non RF individuals. 5. To continue our efforts to isolate and characterize those cardiac antigens cross-reactive with streptococcal antigens and, concomitantly, to identify at a molecular level in our streptococcal gene bank the genes encoding streptococcal antigens cross-reactive with cardiac antigens. Hopefully these studies will advance our knowledge not only in the etiopathogenesis of rheumatic fever but also in other diseases of presumed microbial-host interactions.